As reviewed in last year's annual report, a new and distinct form of the glycolytic enzyme enolase has been isolated and characterized from both rat and human brain. Immunohistochemical studies have established that this protein is strictly localized in neurons and neuroendocrine cells and it has been named Neuron Specific Enolase or NSE. An additional enolase isoenzyme has also been isolated and shown to be localized in glial cells and designated Non-Neuronal Enolase or NNE. These isoenzymes represent the first example of cell specific isoenzyme markers for neurons and glia. Recent efforts have focused on the development of the central nervous sytem, where it has been established that NSE only appears in differentiated neurons. Neuronal differentiation involves an NNE to NSE switch; this phenomenon is being exploited in a wide variety of development neurobiological studies. NSE is also a specific marker for neuroendocrine peptide secreting cells of the APUD class; immunohistochemical studies are in progress in which NSE is being used to map the diffuse neuroendocrine nervous system. Using a sensitive radioimmunoassay, clinical studies of NSE and NNE levels in cerebrospinal fluid and amniotic fluid are being correlated with neuronal and glial pathologies.